Much of the pathology of diabetes occurs in tissues rich in collagen. Among these debilities are premature onset of artherosclerosis, increased lung stiffness, and increased basement membrane thickness. Collagen exists mainly in fibrillar or lamellar forms and intermolecular crosslinks provide the mechanical strength essential to its structural role. There is evidence that the collagen of diabetics is more crosslinked than normal, but the mechanism for this crosslinking is unknown. It has been proposed that non-enzymatic glycosylation of lysine and hydroxylysine on collagen which increases substantially during diabetes may lead to increased crosslinking. Involved in this process may be Maillard browing, a complex series of reactions that gives rise to fluorescent pigments. This process is well known to the food industry because it causes protein crosslinking and loss of nutritional quality in foods upon storage. Crosslink formation will be studied as a function of duration of diabetes in streptozotocin-treated rats. The distribution of crosslinks on the collagen molecule of control tendons will be determined. This will be compared to the distribution observed for diabetic tendons in order to ascertain the sites of non-enzymatic glycosylation and of both normal and abnormal crosslink formation. Maillard reaction products will be recognized by their spectroscopic properties. The effect of diabetes and altered crosslinking on the tensile properties of tendons will be measured. These data will clarify the molecular basis for pathological changes in the physical and biochemical properties of collageneous tissues due to diabetes. The information obtained and the methodology developed as a result of these experiments will be applied to an analysis of tissues from human diabetics when such tissues can be obtained. In addition the results will be applied to the analysis of collagen-containing tissues more complex than tendons such as blood vessels and kidney in order to recognize similar pathological changes in structure.